Table 1.
Polymeric particles as tuberculosis vaccine delivery systems
| First author (Ref) | Year | Polymer | Antigen (s) | Adjuvant (s) | Preparation method | Size | Zeta-Potential (mV) | Route of administration | Animal | Profile of immune responses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Antibody | Cytokine | Challenge | ||||||||||
| Rose et al (21) | 2015 | PLGA (75:25) | MOMP | DDA:TDB (CAF01) | O/W | <250 nm | >5 | Subcutaneous | Female B6C3F1 mice | IgG1 IgG2a IgA | IFN-γ IL-17a IL-5 | NA |
| Carletti et al (22) | 2013 | PLGA (50:50) | Apa | TDM | W/O/W | NA | NA | Subcutaneous Intramuscular | Female BALB/c mice | NA | NA | M. tuberculosis H37Rv |
| Shi et al (23) | 2010 | PLGA (75:25) | TB10.4- Ag85B | MDP-BSA | Emulsion /spray-drying | 3.0µm | −25 | Pulmonary | NA | NA | IL-2 | NA |
| Bivas-Benitaa et al (24) | 2009 | PLGA (53:47) | Rv1733c | PEI | W/O/W | 235 - 275 nm | +38.8 - +64.3 | Intramuscular Intranasal | Female BALB/c mice | NA | IFN-γ IL-12 TNF-α | NA |
| Kirby et al (25) | 2008 | PLGA (75:25) | Ag85B-ESAT-6 | DDA:TDB (CAF01) DDA TDB | W/O/W | 1.50± 0.13 µm | 0-15 | Subcutaneous | Female C57BL/6j mice | IgG1 IgG2b | IFN-γ | NA |
| de Paula et al (26) | 2007 | PLGA (50:50) | HSP65 | TDM | W/O/W | <10 µm | NA | Intratracheal | Female Hartley guinea pigs and Female BALB/c mice | IgG2a | IFN-γ | M. tuberculosis H37Rv |
| Lu et al (27) | 2007 | PLGA (75:25) | rAg85B | MDP TDB | Emulsion /spray-drying | 3.4-4.3 µm | NA | NA | NA | NA | IL-2 | NA |
| Ha et al (28) | 2006 | PLGA (NA) | rAg85A ESAT-6 | IL-12EM AS01B alum | W/O/W | NA | NA | Subcutaneous | Female C57BL/6 mice | Total IgG IgG1 IgG2a | IFN-γ | M. tuberculosis H37Rv |
| Cai et al (29) | 2005 | PLGA (50:50) | Ag85B MPT-64 MPT-83 | DDA | W/O/W | <5 µm | NA | Intramuscular | Female C57BL/6 mice | IgG | IFN-γ | M. tuberculosis H37Rv |
| Evans et al (30) | 2004 | PLGA (50:50) | Mtb8.4 | MPL RC-529 | Hydrophobic ion-pairing technique | 2 µm | NA | Intramuscular Subcutaneous | Female C57Bl/6 mice | IgG IgG2a | IFN-γ | NA |
| Lima et al (31) | 2003 | PLGA (50:50) | HSP65 | TDM | W/O/W | <5 µm | NA | Intramuscular | Female BALB/c mice | IgG1 IgG2a | IFN-γ IL-10 IL-4 | M. tuberculosis H37Rv |
| Lima et al (32) | 2001 | PLGA (50:50) | NA | TDM | W/O/W | NA | NA | Intraperitoneal Intratracheal | Female BALB/c mice | NA | IL-6 TNF-α IL-10 IFN-γ IL-12 IL-4 | M. tuberculosis H37Rv |
| Dhiman et al (33) | 1998 | PLGA (50:50) | 71-kDa cell wall protein | FIA | W/O/W | <0.65 µm | NA | Intramuscular Subcutaneous | NA | NA | NA | M. tuberculosis H37Rv |
| Carpenter et al (34) | 2005 | PLA | ESAT-6 | Alum | W/O/W | 1.179 μm±0.07 | NA | Pulmonary Intranasal Intramuscular | Female BALB/c mice | IgG | IFN-γ IL-4 | NA |
| Venkataprasad et al (35) | 1999 | PLA PLGA (75:25, 50:50) | 38 kDa protein | NA | W/O/W | PLA (3-5 µm) and PLG (0.3-0.8 µm) | NA | Subcutaneous | Female C57BL/10 mice | NA | IFN-γ IL-4 | NA |
| Todoroff et al (36) | 2013 | Poloxamer 407 | Ag85A | CpG oligonucleotide | NA | 27 nm | NA | Pulmonary (Intratracheal) | Female BALB/c mice | IgG, IgG1, and IgG2a | IFN-γ TNF-α IL-2 IL-17a | NA |
| Orr et al (37) | 2014 | NA | ID93 | GLA-SE | NA | < 120 nm | -13 | Intramuscular | Female C57Bl/6 mice | IgG1 IgG2c | IFN-γ TNF-α IL-2 | M. tuberculosis H37Rv |
| Yeboah et al (38) | 2009 | Albumin | Dead whole cells and whole cell lysate | NA | Spray-drying method | 3.52±0.13 µm 6.61±0.70 µm | -13.05 ±19.18 -40.28 ±7.86 | Oral | Rat | IgG IgA | NA | NA |
| Meerak et al (39) | 2013 | Chitosan | Ag85B | NA | Coacervation method | 100–200 nm | NA | Subcutaneous Intranasal | Female BALB/c inbred | total IgG IgG2a | IFN-γ IL-2 IL-4 | NA |
| Feng et al (40) | 2013 | Chitosan | Esat-6/3e-FL | NA | Ionic crosslink and coacervation | 311.2±34 nm | 30.6 mV | Intramuscular Intranasal | Female C57Bl/6 mice | NA | IFN-γ IL-12 IL-10 IL-4 | M. tuberculosis H37Rv |
| Ai et al (41) | 2013 | Chitosan | pHSP65pep | NA | Coacervation method | 350 -400 nm | NA | Intranasal Intradermal | Female BALB/c mice | IgA IgG IgG1 IgG2a | IFN-γ | M. bovis |
| Verma et al (42) | 2013 | Chitosan-TPP | CFP-10 CFP-21 | Ionotropic gelation | 250 -300 nm | 41 ±5.29 | NA | NA | NA | IFN-γ IL-4 | NA | |
| Caetano et al (43) | 2013 | Chitosan/Alginate/TPP | BCG | NA | Ionotropic gelation | 33.865 µm ±5.347 | +10.91 ± 3.55 | Intranasal Subcutaneous | Female BALB/c mice | IgG IgG 1 IgG2a IgA | NA | NA |
| Zhu et al (44) | 2007 | Chitosan | AMM | IFA | Precipitation/coacervation method | 5.78 ± 0.65 µm | 32.77 ± 1.51 | Subcutaneous | Female C57Bl/6 mice | IgG1 IgG2a | IFN-γ IL-4 | NA |
| Bivas-Benita et al (45) | 2004 | Chitosan | DNA vaccine encoding eight HLA-A*0201-restricted T-cell epitopes | NA | Complexation-coacervation method | 376±59 nm | 21±4 | Pulmonary Intramuscular | Female HLA-A2 transgenic mice | NA | IFN-γ | NA |
| Dobakhti et al (46) | 2009 | NA | BCG | Sodium alginate | NA | NA | NA | Subcutaneous | Female BALB/c mice | Total IgG IgG2a IgG1 | IFN-γ | M. bovis |
| Ajdary et al (47) | 2007 | Sodium alginate | BCG | NA | NA | 11.5 μm | NA | Subcutaneous Oral | Female BALB/c mice | Total IgG IgG2a IgG1 | IFN-γ IL-4 | M. bovis |
| Dobakhti et al (48) | 2006 | Calcium alginate | BCG | NA | Internal emulsification method | 11 μm | NA | Subcutaneous Oral | Female BALB/c mice | Total IgG IgG2a IgG1 | NA | NA |
| Wilkinson et al (49) | 2000 | Polystyrene | Ag85A, B and C | NA | NA | 2 μm | NA | NA | NA | NA | IFN-γ | NA |
| Yu et al (50) | 2012 | Fe3O4-Glu-polyethyleneimine | Ag85A-ESAT-6-IL-21 | NA | NA | NA | +36 mV | Intramuscular Subcutaneous | Male C57BL/6 mice | NA | IFN-γ | M. tuberculosis H37Rv |
| Ballester et al (51) | 2011 | Pluronic-stabilized polypropylene sulfide | Ag85B | CpG | Emulsion polymerization and surface functionalized | 30 nm | NA | Intradermal Pulmonary | Female C57BL/6 mice | NA | IFN-γ TNF-α IL-6 IL-1β IL-17a IL-2 | M. tuberculosis Erdman strain |
Abbreviations: O/W: Oil-in-water single emulsion, W/O/W: Double emulsion/solvent evaporation, MOMP: Major outer-membrane protein, Apa: Alanine-proline antigen, MDP: Muramyl dipeptide, BSA: Bovine serum albumin, AS01B: Composed of MPL and QS21 (saponin molecule), RC-529 adjuvant: A synthetic ω-amin-oalkyl-2-amino-2-deoxy-4-phosphono-²-d-glucopyranoside (AGP) which is structurally related to the major hexaacyl component of MPL adjuvant, FIA: Freund’s incomplete adjuvant, ID93: Fusion protein containing M. tuberculosis genes Rv3619, Rv1813, Rv3620, and Rv2608, GLA-SE: A mixture of squalene, DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), poloxamer 188, glycerol, and ammonium phosphate buffer, Esat-6/3e-FL: Esat-6 three T cell epitopes (Esat-6/3e) and fms-like tyrosine kinase 3 ligand (FL) genes, pHSP65pep: pECANS plasmid with four epitopes cast in the gene backbone of HSP65, namely ESAT-664-76, Ag85A124–135, CFP-1055–69, and Ag85B141–153, TPP: Tripolyphosphate, AMM: Ag85B–MPT64190–198–Mtb8.4, Fe3O4-Glu-PEI: Fe3O4-Glutamic acid-Polyethyleneimine, NA: Not available